Cancer is the leading cause of death from disease in children past one year of age in this country. Significant improvement has resulted from treatment regimens designed for the most common forms of childhood malignancy, acute lymphoblastic leukemia. While progress in some of these solid tumors of children has been notable, such as in Wilms' tumor and Hodgkin's disease, the effectiveness of treatment regimens for most childhood tumors has been disappointing. In large part, the difficulties of disease control result from the fact that for many childhood tumors the disease has already disseminated beyond the site of origin at the time of diagnosis. Therefore, for most children with solid tumors a coordinated approach involving surgery, radiotherapy, and chemotherapy is necessary. The role of chemotherapy is extremely important. To this end, this project will develop studies for neuroblastoma, osteosarcoma, and large bowel cancer, to investigate methods of improved therapy. Both clinical and laboratory research will be brought to bear on these disease areas. In addition to these specific disease categories, there will be three general areas of research involving all patients with these tumors. These studies will include Phase I and II drug testing programs, altered drug pharmacokinetics, and epidemiology.